"Purple bacteria are among Earth’s oldest organisms, and among its most efficient in turning sunlight into usable chemical energy. Now, a key to their light-harvesting prowess has been explained through a detailed structural analysis by scientists at MIT.

A ring-shaped molecule with an unusual ninefold symmetry is critical, the researchers found. The circular symmetry accounts for its efficiency in converting sunlight, and for its mechanical durability and strength. The new analysis, carried out by professors of chemistry Jianshu Cao and the late Robert Silbey, postdoc Liam Cleary, and graduate students Hang Chen and Chern Chuang, has been published in the Proceedings of the National Academy of Sciences."

*An intriguing observation of photosynthetic light-harvesting systems is the N-fold symmetry of light-harvesting complex 2 (LH2) of purple bacteria. We calculate the optimal rotational configuration of N-fold rings on a hexagonal lattice and establish two related mechanisms for the promotion of maximum excitation energy transfer (EET). (i) For certain fold numbers, there exist optimal basis cells with rotational symmetry, extendable to the entire lattice for the global optimization of the EET network. (ii) The type of basis cell can reduce or remove the frustration of EET rates across the photosynthetic network. We find that the existence of a basis cell and its type are directly related to the number of matching points S between the fold symmetry and the hexagonal lattice. The two complementary mechanisms provide selection criteria for the fold number and identify groups of consecutive numbers. Remarkably, one such group consists of the naturally occurring 8-, 9-, and 10-fold rings. By considering the inter-ring distance and EET rate, we demonstrate that this group can achieve minimal rotational sensitivity in addition to an optimal packing density, achieving robust and efficient EET. This corroborates our findings i and ii and, through their direct relation to S, suggests the design principle of matching the internal symmetry with the lattice order.*http://bit.ly/1490KnO

Transcriptional biosensors have various applications in metabolic engineering, including dynamic pathway control and high-throughput screening of combinatorial strain libraries. Previously, various biosensors have been created from naturally occurring transcription factors (TFs), largely relying on native sequences with- out the possibility to modularly optimize their response curve. The lack of design and engineering techniques thus greatly hinders the development of custom biosensors. In view of the intended application this is detrimental. In contrast, a bottom-up approach to design tailor-made biosensors was pursued here. Novel biosensors were created that respond to N-acetylneuraminic acid (Neu5Ac), an important sugar moiety with various biological functions, by employing native and engineered promoters that interact with the TF NanR. This bottom-up approach, whereby various tuned modules, e.g., the ribosome binding site (RBS) controlling NanR translation can be combined, enabled the reliable engineering of various response curve characteristics. The latter was validated by testing these biosensors in combination with various Neu5Ac-producing pathways, which allowed to produce up to 1.4 ± 0.4 g/L extracellular Neu5Ac. In this way, the repertoire of biosensors was expanded with seven novel functional Neu5Ac-responsive biosensors.

Synthetic biology has enabled the creation of biological reconfigurable circuits, which perform multiple functions monopolizing a single biological machine; Such a system can switch between different behaviours in response to environmental cues. Previous work has demonstrated switchable dynamical behaviour employing reconfigurable logic gate genetic networks. Here we describe a computational framework for reconfigurable circuits in E.coli using combinations of logic gates, and also propose the biological implementation. The proposed system is an oscillator that can exhibit tunability of frequency and amplitude of oscillations. Further, the frequency of operation can be changed optogenetically. Insilico analysis revealed that two-component light systems, in response to light within a frequency range, can be used for modulating the frequency of the oscillator or stopping the oscillations altogether. Computational modelling reveals that mixing two colonies of E.coli oscillating at different frequencies generates spatial beat patterns. Further, we show that these oscillations more robustly respond to input perturbations compared to the base oscillator, to which the proposed oscillator is a modification. Compared to the base oscillator, the proposed system shows faster synchronization in a colony of cells for a larger region of the parameter space. Additionally, the proposed oscillator also exhibits lesser synchronization error in the transient period after input perturbations. This provides a strong basis for the construction of synthetic reconfigurable circuits in bacteria and other organisms, which can be scaled up to perform functions in the field of time dependent drug delivery with tunable dosages, and sets the stage for further development of circuits with synchronized population level behaviour.

On the 4th of September 2017, the 14th European Conference on Artificial Life (ECAL 2017, Lyon, France) hosted a satellite workshop dedicated to a frontier research question: ‘What can Synthetic Biology offer to (Embodied) Artificial Intelligence (and vice versa)?’ This workshop, as the previous three of the ‘Synthetic Biology (SB)–Artificial Intelligence (AI)’ workshop series, brought together specialists from different disciplines to address the contemporary debate on the evolution of embodied artificial intelligence from a new angle. In a few words: defining the possible roles that SB – an emerging research line combining biology and engineering – can play in the process of establishment of the so-called ‘Embodied paradigm’ in the scientific exploration of cognition and, in particular, in artificial intelligence.

The ultimate goal of synthetic biology is to build customized cells or organisms to meet specific industrial or medical needs. The most important part of the customized cell is a synthetic genome. Advanced genomic writing technologies are required to build such an artificial genome. Recently, the partially-completed synthetic yeast genome project represents a milestone in this field. In this mini review, we briefly introduce the techniques for de novo genome synthesis and genome editing. Furthermore, we summarize recent research progresses and highlight several applications in the synthetic genome field. Finally, we discuss current challenges and future prospects.

Researchers have discovered a single protein that can perform CRISPR-style, precise programmable cutting on both DNA and RNA.

This protein is among the first few Cas9 proteins to work on both types of genetic material without artificial helper components.

CRISPR-Cas9 acts as molecular scissors that can cut DNA at exactly the spot they’re asked to. The technique has transformed research in just five years, making it possible for hundreds of teams of scientists to snip out portions of a chromosome that are mutated, or to see what happens when a certain gene isn’t there. But CRISPR-Cas9 can’t cut the other kind of genetic material found in cells known as RNA.

Now, an initial biochemical study in laboratory test tubes, published in the journal Molecular Cell, shows the promise of the new CRISPR approach using the protein called NmeCas9. It’s derived from Neisseria meningitidis, the bacteria that cause some of the most severe and deadly cases of meningitis each year.

The team is working to test the tool in living bacteria cells to see if NmeCas9 achieves the same effect that they saw in test tubes. They hope to eventually progress to human cells. If it works, NmeCas9 could help expand the role of CRISPR in studying—and perhaps intervening—in many diseases.

“All that has been achieved with CRISPR-Cas9 to manipulate the chromosomes we might be able to do at the RNA level.”“The fact that our protein has dual function—able to target both DNA and RNA—gives us the opportunity to develop platforms to do dual targeting,” says Yan Zhang, assistant professor of biological chemistry at the University of Michigan who led the research team. “It may make it possible to perform CRISPR cutting on both RNA and DNA at once, or alternatively just on single-stranded messenger RNA without affecting genomic regions at all.”

In cells, the DNA contained in chromosomes acts as the permanent encyclopedia of instructions for making everything the cell needs. But to actually make anything, cells need RNA transcribed from the chromosomes.

One of RNA’s most important functions in cells is the “photocopying” of stretches of DNA, so that machines within the cell can read the instructions and make proteins. Many diseases arise from problems with cellular RNAs.

The new technique aims to produce a pair of universal genetic scissors. And, because NmeCas9 is a much smaller protein than other Cas9 proteins used in CRISPR editing, they hope it will be more useful.

Zhang and co-first authors Beth A. Rousseau and Zhonggang Hou developed and tested the NmeCas9 protein in their lab at the University of Michigan Medical School.

Imagine zippers and scissors

To understand CRISPR in simpler terms, imagine a pair of scissors that have one side of a zipper attached to the tip of the blades. In order to cut a stretch of DNA at exactly the right spot, the zipper has to match up exactly with a stretch of DNA leading up to that spot—forming a tight bond that positions the scissors in just the right place.

In CRISPR, the “zipper” is made of specially designed RNA, and the “scissor” effect comes from harnessing the natural cutting action of a protein, or enzyme, called Cas9. The CRISPR revolution has made it possible to design unique RNA zippers that can attach to specific genes that play a role in a disease, and cut them out.

Still, the technology has yet to be widely used in people.

The first human clinical trials using CRISPR to cut a flawed section of DNA are reported to be underway in China, and preparing to begin in the United States.

Research is also ongoing to see if human embryos containing disease-related genetic mutations can be changed through CRISPR, although there is controversy about the ethical implications of this practice, known as “germline editing.”

A great accident

The discovery of NmeCas9 happened by accident when the team was studying the basic function of the NmeCas9 protein in cutting DNA. The team was using RNA as the comparison, or a control sample—but noticed that it was getting cut, too.

Digging deeper, they discovered the dual-cutting function of NmeCas9 and began testing it biochemically.

In addition to their discovery, they’re aware that two other groups are either preparing to report or have just reported Cas9 proteins from other bacteria that can carry out RNA targeting without any stimulatory co-factors, unlike previous RNA-editing CRISPR-Cas9 techniques.

Using CRISPR against cancer shows success in mice

“If NmeCas9 works in live cells as it has in vitro, we can develop it as a tool to edit the messenger RNA transcript, which means we might be able to block a gene product without manipulating the gene itself,” says Zhang. “We might also be able to harness it as a research tool to deliver fluorescent markers to specific RNA sequences, or to block events like RNA splicing.

“All that has been achieved with CRISPR-Cas9 to manipulate the chromosomes we might be able to do at the RNA level.”

Funding for the work came from the National Institutes of Health and by the University of Michigan Medical School’s Biological Sciences Scholars Program.

Airplane flight recorders and body cameras help investigators make sense of complicated events. Biologists studying cells have tried to build their own data recorders, for example by linking the activity of a gene of interest to one making a fluorescent protein. Their goal is to clarify processes such as the emergence of cancer, aging, environmental impacts, and embryonic development. A new cellular recorder that borrows from CRISPR, the revolutionary genome editing tool, now offers what could be a better taping device that captures data on DNA.

In Science online this week, chemist David Liu and postdoc Weixin Tang, both of Harvard University, unveil two forms of what they call a CRISPR-mediated analog multievent recording apparatus, or CAMERA. In proof-of-concept experiments, they show in both bacterial and human cells how this tool can record exposure to light, antibiotics, and viral infection or document internal molecular events. "The study highlights the really creative ways people are harnessing discoveries in CRISPR to build these synthetic pathways," says Dave Savage, a protein engineer at the University of California, Berkeley.

Other investigators have created recording devices with CRISPR components, among them Timothy Lu of the Massachusetts Institute of Technology in Cambridge. But Lu notes that his system was limited to bacteria, and compared with CAMERA it required "an order of magnitude" more cells to reliably record signals and had a much poorer signal-to-noise ratio. The new work, he says, "is really beautiful stuff" and has "a level of efficiency and precision that goes beyond what we did earlier." (Lu this week plans to release a preprint describing a system similar to one version of CAMERA.)

Synthetic cells, artificial cell-like particles, capable of autonomously synthesizing RNA and proteins based on a DNA template, are emerging platforms for studying cellular functions and for revealing the origins-of-life. Here, it is shown for the first time that artificial lipid-based vesicles, containing the molecular machinery necessary for transcription and translation, can be used to synthesize anticancer proteins inside tumors. The synthetic cells are engineered as stand-alone systems, sourcing nutrients from their biological microenvironment to trigger protein synthesis. When pre-loaded with template DNA, amino acids and energy-supplying molecules, up to 2 × 107 copies of green fluorescent protein are synthesized in each synthetic cell. A variety of proteins, having molecular weights reaching 66 kDa and with diagnostic and therapeutic activities, are synthesized inside the particles. Incubating synthetic cells, encoded to secrete Pseudomonas exotoxin A (PE) with 4T1 breast cancer cells in culture, resulted in killing of most of the malignant cells. In mice bearing 4T1 tumors, histological evaluation of the tumor tissue after a local injection of PE-producing particles indicates robust apoptosis. Synthetic cells are new platforms for synthesizing therapeutic proteins on-demand in diseased tissues.

Society’s strong dependence on fossil fuels and petroleum-based products leads not only to a rapid decline of natural oil reserves but contributes massively to global warming and environmental damage. This consequently urges society to look into more sustainable alternatives. Microorganisms present such sustainable alternative if converted into so-called microbial cell factories. Instead of crude oil, cell factories use renewable resources or waste products as source material. The challenge is, however, that microbial production needs to be economically feasible to compete with the classical chemical production. The development of a microbial cell factory typically takes up to 8 years of research and costs over $50 million. The production and selection of heterologous pathway proteins are major bottlenecks encountered in the construction of a cell factory. Thus, new approaches for the optimization of recombinant protein production and screening techniques with high capacity for the identification of the best performing enzymes are continually developed. This thesis aims to equip researchers with a fundamental knowledge about protein biosynthesis necessary for the understanding of protein production bottlenecks. Moreover, the thesis guides through the possible causes of low protein yields and presents available approaches for optimization of the protein and the host. The main work presented in this thesis provides and applies a new synthetic biology approach for the optimization and selection of recombinant proteins. A major bottleneck during production is translation initiation. By creating sequence libraries of the translation initiation region, protein production can be improved substantially in Gram-negative and Gram-positive bacteria. The design of versatile and tuneable translational coupling devices and their fusion to antibiotic selection markers enables subsequent selection of high-expressing constructs. The approach is a simple and inexpensive alternative to advanced screening techniques. In addition, a second synthetic biology approach provides the means for fast and efficient plasmid backbone swapping and is a versatile tool for the design and construction of optimal protein production constructs.

Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.

Synthetic biology is a rapidly growing multidisciplinary branch of science which aims to mimic complex biological systems by creating similar forms. Constructing an artificial system requires optimization at the gene and protein levels to allow the formation of entire biological pathways. Advances in cell-free synthetic biology have helped in discovering new genes, proteins, and pathways bypassing the complexity of the complex pathway interactions in living cells. Furthermore, this method is cost- and time-effective with access to the cellular protein factory without the membrane boundaries. The freedom of design, full automation, and mimicking of in vivo systems reveal advantages of synthetic biology that can improve the molecular understanding of processes, relevant for life science applications. In parallel, in vitro approaches have enhanced our understanding of the living system. This review highlights the recent evolution of cell-free gene design, proteins, and cells integrated with microfluidic platforms as a promising technology, which has allowed for the transformation of the concept of bioprocesses. Although several challenges remain, the manipulation of biological synthetic machinery in microfluidic devices as suitable 'homes' for in vitro protein synthesis has been proposed as a pioneering approach for the development of new platforms, relevant in biomedical and diagnostic contexts towards even the sensing and monitoring of environmental issues.

Phenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the importance of gut microbes in digestion, a genetically engineered microbe could potentially degrade some ingested phenylalanine from the diet prior to absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined conditions for freeze-drying and delivery of bacteria. Animals showed reduced blood phe within three to four days of treatment with pHENOMMenal probiotic, and blood phe concentrations remained significantly reduced (P < 0.0005) compared to untreated controls during the course of experiments. Although pHENOMMenal probiotic could be cultured from fecal samples at four months post treatment, it could no longer be cultivated from feces at eight months post treatment, indicating eventual loss of the microbe from the gut. Preliminary screens during experimentation found no immune response to AvPAL. Collectively these studies provide data for the use of a genetically engineered probiotic as a potential treatment for PKU.

Synthetic biology is a novel branch of biological sciences. The creation of a synthetic microorganisms with minimal genome compatible with life by Craig Venter had provoked the prior hot philosophical discussions about the nature of life. The recent advancements in synthetic biology brings new philosophical analysis about hybrid entities “synthetic organisms” and “living machines” and fundamental difference between biological machines and the living world. This paper is a critical analysis of the philosophical perspective on the design of synthetic organisms, minimal genome and artificial life. It also presents a critical view on knowledge-making practices in synthetic biology on Richard Feynman’s statement: “What I cannot create, I do not understand.”

BACKGROUND:When using the microbial cell factories for green manufacturing, several important issues need to be addressed such as how to maintain the stability of biocatalysts used in the bioprocess and how to improve the synthetic efficiency of the biological system. One strategy widely used during natural evolution is the creation of organelles which can be used for regional control. This kind of compartmentalization strategy has inspired the design of artificial organelle-like nanodevice for synthetic biology and "green chemistry".RESULTS:Mimicking the natural concept of functional compartments, here we show that the engineered thermostable ketohydroxyglutarate aldolase from Thermotoga maritima could be developed as a general platform for nanoreactor design via supramolecular self-assembly. An industrial biocatalyst-(+)-γ-lactamase was selected as a model catalyst and successful encapsulated in the nanoreactor with high copies. These nanomaterials could easily be synthesized by Escherichia coli by heterologous expression and subsequently self-assembles into the target organelle-like nanoreactors both in vivo and in vitro. By probing their structural characteristics via transmission electronic microscopy and their catalytic activity under diverse conditions, we proved that these nanoreactors could confer a significant benefit to the cargo proteins. The encapsulated protein exhibits significantly improved stability under conditions such as in the presence of organic solvent or proteases, and shows better substrate tolerance than free enzyme.CONCLUSIONS:Our biodesign strategy provides new methods to develop new catalytically active protein-nanoreactors and could easily be applied into other biocatalysts. These artificial organelles could have widely application in sustainable catalysis, synthetic biology and could significantly improve the performance of microbial cell factories.

Introduction: The discovery and domestication of biomolecules that respond to light has taken a light of its own, providing new molecular tools with incredible spatio-temporal resolution to manipulate cellular behavior.

Areas covered: The authors herein analyze the current optogenetic tools in light of their current, and potential, uses in cancer drug discovery, biosafety and cancer biology.

Expert opinion: The pipeline from drug discovery to the clinic is plagued with drawbacks, where most drugs fail in either efficacy or safety. These issues require the redesign of the pipeline and the development of more controllable/personalized therapies. Light is, aside from inexpensive, almost harmless if used appropriately, can be directed to single cells or organs with controllable penetration, and comes in a variety of wavelengths. Light-responsive systems can activate, inhibit or compensate cell signaling pathways or specific cellular events, allowing the specific control of the genome and epigenome, and modulate cell fate and transformation. These synthetic molecular tools have the potential to revolutionize drug discovery and cancer research.

Bacteria and bacteriophages arm themselves with various defensive and counterdefensive mechanisms to protect their own genome and degrade the other’s. CRISPR (clustered regularly interspaced short palindromic repeat)–Cas (CRISPR-associated) is an adaptive bacterial defense mechanism that recognizes short stretches of invading phage genome and destroys it by nuclease attack. Unexpectedly, we discovered that the CRISPR-Cas system might also accelerate phage evolution. When Escherichia coli bacteria containing CRISPR-Cas9 were infected with phage T4, its cytosine hydroxymethylated and glucosylated genome was cleaved poorly by Cas9 nuclease, but the continuing CRISPR-Cas9 pressure led to rapid evolution of mutants that accumulated even by the time a single plaque was formed. The mutation frequencies are, remarkably, approximately six orders of magnitude higher than the spontaneous mutation frequency in the absence of CRISPR pressure. Our findings lead to the hypothesis that the CRISPR-Cas might be a double-edged sword, providing survival advantages to both bacteria and phages, leading to their coevolution and abundance on Earth.

Vast potential exists for the development of novel, engineered platforms that manipulate biology for the production of programmed advanced materials. Such systems would possess the autonomous, adaptive, and self-healing characteristics of living organisms, but would be engineered with the goal of assembling bulk materials with designer physicochemical or mechanical properties, across multiple length scales. Early efforts toward such engineered living materials (ELMs) are reviewed here, with an emphasis on engineered bacterial systems, living composite materials which integrate inorganic components, successful examples of large-scale implementation, and production methods. In addition, a conceptual exploration of the fundamental criteria of ELM technology and its future challenges is presented. Cradled within the rich intersection of synthetic biology and self-assembling materials, the development of ELM technologies allows the power of biology to be leveraged to grow complex structures and objects using a palette of bio-nanomaterials.

Sharing your scoops to your social media accounts is a must to distribute your curated content. Not only will it drive traffic and leads through your content, but it will help show your expertise with your followers.

Integrating your curated content to your website or blog will allow you to increase your website visitors’ engagement, boost SEO and acquire new visitors. By redirecting your social media traffic to your website, Scoop.it will also help you generate more qualified traffic and leads from your curation work.

Distributing your curated content through a newsletter is a great way to nurture and engage your email subscribers will developing your traffic and visibility.
Creating engaging newsletters with your curated content is really easy.